A major gene controlling expression of endogenous xenotropic murine leukemia viruses (x-MuLV) was mapped to the I-C region of the H-2 complex. The gene, termed Cxv-1, has an alletle permissive for high levels of virus expression in mice bearing the H-2p haplotype whereas most other strains carry a restrictive allete at this locus. The gene appears to determine the levels of expression of infectious virus from virus-inducing loci on chromosome 1. An extract from the spleen of a lymphomatous mice infected with the wild mouse ecotromic MuLV, CAS-BR-M, induced erythroleukemias in newborn mice after a latent period of 4 to 12 weeks. The extracts were found to contain a defective agent similar to but distinct from the spleen focus forming virus of the Friend MuLV complex. Other extracts which do not contain defective MuLV were found to rapidly induce lymphomas. NFS mice, congenic for ecotropic MuLV loci, and SJL mice develop splenic lymphomas previously characterized as reticullum cell sarcoma, Type B. Tumors from both sets of mice were shown to bear cell surface antigens characteristic of cells in the B lymphocyte lineage.